Publications

Policy Points The rate of adoption of chronic care management processes (CMPs) by physician organizations has been fairly slow in spite of demonstrated effectiveness of CMPs in improving outcomes of chronic care. Exnovation (ie, removal of innovations) by physician organizations largely explains the slow population‐level increases in practice use of CMPs over time. Expanded health information technology functions may aid practices in retaining CMPs. Low provider reimbursement by Medicaid programs, however, may contribute to disinvestment in CMPs by physician organizations. Context Exnovation is the process of removal of innovations that are not effective in improving organizational performance, are too disruptive to routine operations, or do not fit well with the existing organizational strategy, incentives, structure, and/or culture. Exnovation may contribute to the low overall adoption of care management processes (CMPs) by US physician organizations over time. Methods Three national surveys of US physician organizations, which included common questions about organizational characteristics, use of CMPs, and health information technology (HIT) capabilities for practices of all sizes, and Truven Health Insurance Coverage Estimates were integrated to assess organizational and market influences on the exnovation of CMPs in a longitudinal cohort of 1,048 physician organizations. CMPs included 5 strategies for each of 4 chronic conditions (diabetes, asthma, congestive heart failure, and depression): registry use, nurse care management, patient reminders for preventive and care management services to prevent exacerbations of chronic illness, use of nonphysician clinicians to provide patient education, and quality of care feedback to physicians. Findings Over one‐third (34.1%) of physician organizations exnovated CMPs on net. Quality of care data feedback to physicians and patient reminders for recommended preventive and chronic care were discontinued by over one‐third of exnovators, while nurse care management and registries were largely retained. Greater proportions of baseline Medicaid practice revenue (incidence rate ratio [IRR] = 1.44, p < 0.001) and increasing proportions of revenue from Medicaid (IRR = 1.02, p < 0.05) were associated with greater CMP exnovation by physician organizations on net. Practices with greater expansion of HIT functionality exnovated fewer CMPs (IRR = 0.91, p < 0.001) compared to practices with less expansion of HIT functionality. Conclusions Exnovation of CMPs is an important reason why the population‐level adoption of CMPs by physician organizations has remained low. Expanded HIT functions and changes to Medicaid reimbursement and incentives may aid the retention of CMPs by physician organizations.

Synthetic zinc finger proteins (ZFPs) can be created to target promoter DNA sequences, repressing transcription. The binding of small RNA (sRNA) to ZFP mRNA creates an ultrasensitive response to generate higher effective Hill coefficients. Here we combined three "off the shelf" ZFPs and three sRNAs to create new modular inverters in E. coli and quantify their behavior using induction fold. We found a general ordering of the effects of the ZFPs and sRNAs on induction fold that mostly held true when combining these parts. We then attempted to construct a ring oscillator using our new inverters. Our chosen parts performed insufficiently to create oscillations, but we include future directions for improvement upon our work presented here.

Abstract Modeling the dynamic behavior of fluid movement in an oil reservoir is complicated because of non-linear interactions between reservoir heterogeneity and fluid flow. Simple regression, geostatistical, and numerical simulation techniques have been used in the past to model fluid movement with various degrees of success. Most of these methods, however, suffer from common drawbacks that they are time consuming and difficult to automate. This paper presents a new method based on artificial neural networks (ANNs) to model dynamic gas-oil contacts in the Prudhoe Bay reservoir. This method is fast, efficient, and highly automated and requires minimum user intervention. The proposed method uses oil, gas, and water production, perforation history, permeability, sand and shale distribution, and surveillance data at surrounding wells as ANN input to predict the fluid distribution a t a target well. A two-step method is developed to design an ANN. The first step trains the network using previously measured data as input and output, and thus establishing the internal rules of the network. The second step uses the trained network to estimate the fluid distribution at target wells. Results show that the ANN method can predict fluid distribution at target wells more accurately and consistently than conventional methods.

MDM2 and MDMX, negative regulators of the tumor suppressor p53, can work separately and as a heteromeric complex to restrain p53's functions. MDM2 also has pro-oncogenic roles in cells, tissues, and animals that are independent of p53. There is less information available about p53-independent roles of MDMX or the MDM2–MDMX complex. We found that MDM2 and MDMX facilitate ferroptosis in cells with or without p53. Using small molecules, RNA interference reagents, and mutant forms of MDMX, we found that MDM2 and MDMX, likely working in part as a complex, normally facilitate ferroptotic death. We observed that MDM2 and MDMX alter the lipid profile of cells to favor ferroptosis. Inhibition of MDM2 or MDMX leads to increased levels of FSP1 protein and a consequent increase in the levels of coenzyme Q 10 , an endogenous lipophilic antioxidant. This suggests that MDM2 and MDMX normally prevent cells from mounting an adequate defense against lipid peroxidation and thereby promote ferroptosis. Moreover, we found that PPARα activity is essential for MDM2 and MDMX to promote ferroptosis, suggesting that the MDM2–MDMX complex regulates lipids through altering PPARα activity. These findings reveal the complexity of cellular responses to MDM2 and MDMX and suggest that MDM2–MDMX inhibition might be useful for preventing degenerative diseases involving ferroptosis. Furthermore, they suggest that MDM2/MDMX amplification may predict sensitivity of some cancers to ferroptosis inducers.

This direct kinetic assessment confirms a course of spermatogenesis that is on the shorter side of traditional estimates based on prior analyses. In addition, the variability observed in healthy men suggests that characteristics such as the epididymal reservoir effect may influence the modeling of in vivo spermatogenesis.

Herein, we demonstrate the first example of a multistep solid-state organic synthesis, in which a new imine-linked two-dimensional covalent organic framework (COF-170, <b>1</b>) was transformed through three consecutive postsynthetic modifications into porous, crystalline cyclic carbamate and thiocarbamate-linked frameworks. These linkages are previously unreported and inaccessible through <i>de novo</i> synthesis. While not altering the overall connectivity of the framework, these chemical transformations induce significant conformational and structural changes at each step, highlighting the key importance of noncovalent interactions and conformational flexibility to COF crystallinity and porosity. These transformations were assessed using ¹⁵N multiCP-MAS NMR spectroscopy, providing the first quantitation of yields in COF postsynthetic modification reactions, as well as of amine defect sites in imine-linked COFs. This multistep COF linkage postsynthetic modification represents a significant step toward bringing the precision of organic solution-phase synthesis to extended solid-state compounds.

Metabolic engineering was applied to the development of Escherichia coli capable of synthesizing tyrosol (2-(4-hydroxyphenyl)ethanol), an attractive phenolic compound with great industrial value, from glucose, a renewable carbon source. In this strain, tyrosine, which was supplied not only from the culture medium but also from the central metabolism, was converted into tyrosol via three steps: decarboxylation, amine oxidation, and reduction. The engineered strain synthesized both tyrosol and 4-hydroxyphenylacetate (4HPA), but disruption of the endogenous phenylacetaldehyde dehydrogenase gene shut off 4HPA production and improved the production of tyrosol as a sole product. The engineered mutant strain was capable of producing 0.5 mM tyrosol from 1% (w/v) glucose during a 48 h shake flask cultivation.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.